US10112193B2 - Fabrication of a microfluidic chip package or assembly with separable chips - Google Patents
Fabrication of a microfluidic chip package or assembly with separable chips Download PDFInfo
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- US10112193B2 US10112193B2 US14/901,685 US201414901685A US10112193B2 US 10112193 B2 US10112193 B2 US 10112193B2 US 201414901685 A US201414901685 A US 201414901685A US 10112193 B2 US10112193 B2 US 10112193B2
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00865—Multistep processes for the separation of wafers into individual elements
- B81C1/00888—Multistep processes involving only mechanical separation, e.g. grooving followed by cleaving
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0883—Serpentine channels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
Definitions
- the invention relates in general to the fabrication of microfluidic chip package or assembly. It is in particular directed to methods of fabrication of several microfluidic chips on a same wafer.
- Microfluidics generally refers to microfabricated devices, which are used for pumping, sampling, mixing, analyzing and dosing liquids. Prominent features thereof originate from the peculiar behavior that liquids exhibit at the micrometer length scale. Flow of liquids in microfluidics is typically laminar. Volumes well below one nanoliter can be reached by fabricating structures with lateral dimensions in the micrometer range. Reactions that are limited at large scales (by diffusion of reactants) can be accelerated. Finally, parallel streams of liquids can possibly be accurately and reproducibility controlled, allowing for chemical reactions and gradients to be made at liquid/liquid and liquid/solid interfaces. Microfluidics are accordingly used for various applications in life sciences. Microfluidic devices microfluidic are commonly called microfluidic chips.
- microfluidic-based bioassays require passing a liquid sample inside a microfluidic flow path.
- the flow conditions are important as they impact the outcome of the assay. While several methods and devices for flowing liquids inside microfluidic flow paths have been developed, these methods either lack flexibility or operate with a limited type of samples and flow conditions.
- microfluidics generally have deep structures, i.e., around a few micrometer, up to 20 micrometers or even deeper. In many cases, 5 micrometers is already considered as a small depth in microfluidic applications because such a small depth can generate a large hydraulic resistance on a liquid and can block or become clogged with microbeads and particles, such a small depth can also be incompatible with samples containing cells. As a result, existing semiconductor wafer processes are challenged by, if not incompatible with the requirements needed for microfluidic chip fabrication both in terms of manufacturing processes and cost of fabrication.
- the present invention is embodied as a method of fabrication of a microfluidic chip package or assembly, comprising:
- the substrate provided has several blocks, each comprising one or more microfluidic structures on a face of the substrate; the applied cover-film covers said several blocks; and the partial cuts obtained and the cover-film applied are such as to enable singulation of each of said several blocks.
- partially cutting into the substrate is carried out such that a residual thickness of the substrate after partially cutting makes it possible to separate said at least one block by hand, preferably by cleaving said at least one block.
- the cover-film applied comprises openings forming patterns corresponding to structures of the microfluidic chip assembly already present or to be subsequently fabricated.
- the cover-film applied is a dry-film resist, and, preferably, the cover-film fulfills one or more of the following conditions: it comprises an epoxy resin, it is a laminate sheet, and has a Young's modulus between 3 and 5 gigapascal.
- a thickness of the dry-film resist applied is between 10 and 100 ⁇ m, and preferably between 30 and 70 ⁇ m.
- applying the cover film comprises: providing a film comprising at least two layers, including the cover film and a backing film; applying the cover film against an exposed surface on said face of the substrate by pressing the backing film, preferably by laminating the backing film; and removing the backing film.
- providing the film further comprises patterning the cover film, preferably by one of: photolithography; cutting; punching; or laser ablation, prior to applying the patterned cover film, to obtain a cover film that comprises openings forming patterns corresponding to structures of the microfluidic chip assembly already present or to be subsequently fabricated.
- At least one block of the substrate provided exhibits a microfluidic microchannel on said face, the average depth or cross-sectional diameter of the microchannel being between 5 and 50 micrometers, and preferably between 10 and 20 micrometers.
- the method further comprises, after cleaning and before applying the cover-film, a step of depositing reagents in one or more of the microfluidic structures, wherein depositing reagents preferably comprises depositing at least two types of reagents in microfluidic structures of at least two different blocks of the substrate, respective, or within one or more microstructures of a same block.
- the invention is embodied as a microfluidic chip package or assembly comprising:
- the cover film is a dry-film resist and has a thickness between 20 and 100 ⁇ m, preferably between 30 and 70 ⁇ m.
- the cover film comprises openings forming patterns corresponding to microfluidic structures of the one or more blocks, said microfluidic structures being one or more of:
- the invention is embodied as a use of such a microfluidic chip package or assembly, wherein: the microfluidic chip assembly is provided to a recipient; and the recipient separates at least one of said one or more blocks from the assembly.
- the invention is embodied as a microfluidic chip obtainable according to the above methods or from the above microfluidic chip packages or assemblies, by separating a covered block from the package or assembly, the chip comprising a covered block and exhibiting residual marks of partial cut and residual marks of singulation, such as cleavage planes or parting breaks, at a periphery thereof.
- FIGS. 1 to 8 schematically illustrate high-level steps of methods of fabrication, according to embodiments. Each step is illustrated using a schematic, partial depiction of a cross-section of a chip package or assembly, focusing on one block thereof.
- FIGS. 1 a , 2 a , 5 a and 8 a are 3D (schematic) views corresponding to FIGS. 1, 2, 5 and 8 respectively;
- FIG. 9 is a photograph illustrating a singulation of one chip, as otherwise illustrated in FIG. 8 ), and as involved in embodiments;
- FIGS. 10( a )-( d ) are photographs illustrating steps S 1 , S 3 , S 5 and S 8 (also illustrated in FIGS. 1, 3, 5 and 8 ), respectively, as involved in embodiments.
- FIG. 11 is an image of a slightly tilted microfluidic chip, showing diced (top) and cleaved (bottom) parts of a microfluidic chip, according to embodiments.
- each covered block shall correspond to a microfluidic chip (possibly ready for use), after singulation.
- step S 2 “cutting” is to be interpreted broadly: the partial cut may be carried out by mechanically sawing e.g., using a dicing saw (as depicted in FIG. 2 a ), wire saw, etc., or still by scribing or laser cutting, etc.
- the cutting step S 2 can typically be carried out by cutting transversely to an average plane of the substrate. It gives rise to partial cuts 10 c extending into the thickness of the substrate 10 , 30 , and notably into the thickness of a main component, e.g., a main body 10 of the substrate.
- the partial cut is preferably carried out from above (as illustrated in FIG. 2 a ), from the same side exhibiting the microstructures; the uncut residual portion 10 r is a lower portion in that case.
- opaque substrates such as silicon
- the regions to be cut can be marked by patterns (dicing marks) fabricated during the microchannel or microelectrode (if present) fabrication.
- the cutting can be carried out from either side since the dicing marks are visible from both sides. In this case, the exposed side F of the substrate may not have to be protected by an additional protective film since the dicing tape may already act as such.
- step S 2 implicitly involves cutting along a periphery of the blocks, i.e., to later enable singulation thereof, as best seen in FIG. 2 a .
- the cut lines 10 c enable subsequent singulation of the blocks.
- contiguous dashed cut lines may suffice, the cuts being through holes or not, but this would substantially complicate the cutting step.
- dicing usually means separating dies from a wafer following wafer processing, i.e., the wafer is fully cut through.
- the substrate is preferably an essentially planar, typically layered support structure comprising, in addition to a main body 10 (e.g., a wafer), one or more layers 30 , 32 covering the body 10 .
- Layers 30 typically comprise thin layers, which may comprise a material such as a metal or an oxide, i.e., distinct from the material of the body 10 .
- the substrate may further comprise a layer 32 such as a photopatterned dry-film resist 32 (e.g., PerMX3020) or patterned photoresist, for example SU-8, in which microfluidic structures 20 are defined.
- a photopatterned dry-film resist 32 e.g., PerMX3020
- patterned photoresist for example SU-8
- microstructures are assumed to be grooved, e.g., etched, in the substrate 10 , 30 , whereas in the embodiment of FIG. 11 , microstructures such as microchannel 20 are defined in a photopatterned dry-film resist 32 .
- the body 10 is preferably mounted on a dicing tape 11 prior to cutting S 2 , the dicing tape opposite to the microfluidic structures.
- the tape 11 may have a sticky backing to hold the body 10 , e.g., on a thin sheet metal frame.
- the dicing tape 11 may more generally be any structure supporting the body 10 , to hold and preserve the body while cutting S 2 .
- the tape 11 is typically removed after cutting S 2 as it is usually not compatible with cleaning solvents.
- a protective photoresist layer may be applied before cutting, e.g., for protection; and if so, it shall be removed before or during cleaning.
- the whole substrate can be cleaned, step S 4 , after cutting.
- the cleaning step S 4 shall preferably involve rinsing and drying the substrate as well.
- the assembly 1 including any microstructure thereon may undergo a surface treatment, be functionalized, etc., depending on the application desired.
- the following steps S 5 -S 7 aim at applying a cover-film to cover the microfluidic structures and possibly complete them e.g., close the channels 20 in each block.
- a single cover film is applied to cover all microstructures on the substrate, though multiple layers can be contemplated too, if necessary.
- the cover film 62 is thus applied at substrate-level too, after partially cutting S 2 and cleaning S 4 , and before any subsequent singulation step S 8 .
- the cover film 62 must be distinguished from a protective photoresist film that can otherwise be applied before cutting S 2 and removed after. Indeed, protective films are usually applied before dicing to protect a processed wafer.
- the cover film 62 is applied after cutting and cleaning (e.g., after having rinsed, cleaned and dried) the partially cut substrate, clean microfluidic structures are obtained for the whole assembly, i.e., at substrate level, a thing that so far was only carried out at chip level.
- the above solution is all the more advantageous when cutting S 2 , cleaning S 4 , surface treatment (if any) and reagent integration S 4 a (if any), e.g., any one or more of the steps occurring prior to sealing, is to be carried out in a wet environment.
- the assembly can be singulated and the resulting dies can be readily used.
- the chip and cover can also be sterilized using chemicals such as 70% ethanol before sealing the chip and chip singulation. Therefore, the risk of adversary filling of liquids into the closed channels during cutting and surface preparation is prevented.
- the method may thus comprise an intermediate step S 4 a of depositing reagents in one or more of the microfluidic structures e.g., microchannels.
- devices according to embodiments may include such reagents in microstructures.
- one may for instance add solutions containing reagents in microchannels using an inkjet spotter and dry the reagents.
- Lamination of a dry film resist at low temperature e.g., approximately 45 degrees
- An opportunity is thus offered for integrating reagents before covering the device with the cover-film 62 . Different reagents could be deposited in respective blocks 14 , 14 a , or even within different microstructures 20 of a same block. This opportunity opens the way to large-scale production of biochemically functionalized microfluidic devices.
- the substrate 10 , 30 preferably has several blocks 14 , 14 a , which comprise, each, microfluidic structures (machined or otherwise provided on face F of the substrate, FIGS. 1, 1 a .
- the applied cover-film 62 covers all blocks 14 , 14 a .
- the partial cuts 10 c obtained and the cover-film 62 applied are such as to still enable singulation of the blocks 14 , 14 a .
- only one block is provided; an the method restricts to the fabrication of a specific package in that case, where outer lateral portions of substrate, i.e., beyond the partial cuts, serve to better protect, manipulate and transport the unique block in that case.
- the step of partially cutting S 2 into the substrate is preferably carried out such that a residual thickness 10 r of the substrate after partially cutting S 2 makes it possible to separate the blocks by hand, e.g., by cleaving the blocks 14 , 14 a .
- the body 10 e.g., a Si wafer, typically is the main mechanical support of the chip assembly, such that mechanical properties of the assembly (starting with robustness) are mainly determined by the body 10 .
- the residual thickness 10 r , after cutting S 2 , of the body 10 (and more generally of the substrate 10 , 30 as a whole) at the level of the partial cuts 10 c must be such as to enable subsequent singulation by hand in that case.
- FIG. 2 a Since several chips are manufactured from a same wafer, for efficiency, partial cuts are carried out around each block 14 , 14 a , see FIG. 2 a .
- the residual thickness 10 r of the body 10 after cutting can be tuned ( FIG. 2 ), depending on the materials involved, to make it cleavable by hand: any user could thus proceed to the singulation, as illustrated in FIG. 9 .
- Lateral assemblies of chips, i.e., blocks 14 , 14 a can thus be provided to users as a single object. The user can then separate the blocks without any equipment.
- a single block 14 could be provided to a user, surrounded by inactive lateral substrate portions, which are partially separated from the single block by partial cuts 10 c that enable singulation.
- the partial cuts are preferably obtained at the level of an inactive region.
- further optimization of the manufacture process may lead to design some of the functional features extending from one block 14 to another, contiguous block 14 a , such as electrical contacts or air vents, which can possibly be cut S 2 , e.g., in halves. This provides, in fine, electrical contacts, air vents, etc. for two or more contiguous dies, a thing that may simplify the manufacture steps and allows for saving space on the initial substrate.
- the initial wafer thickness t i typically depends on the wafer size e.g., 525 ⁇ m for 4-inch wafers to 775 ⁇ m for 12-inch wafers. Best results have for instance been obtained for 4-inch Si wafers that had been partially cut to about 250-300 ⁇ m.
- a satisfactory trade-off typically is to obtain residual thicknesses that after partially cutting are less than 500 ⁇ m, and more preferably less than 300 ⁇ m for Si wafers.
- a 300 to 350 ⁇ m cutting depth, typically 50 ⁇ m more than for a Si wafer, is preferred, to achieve easier breaking as glass does not have crystallographic planes.
- the cover-film applied S 5 -S 7 may comprise openings 62 o that form patterns corresponding to structures of the microfluidic chip assembly, already present or subsequently fabricated.
- the cover film may thus be designed to favor subsequent fabrication steps of other microfluidic structures like air vents, liquid loading pads, electrical contacts, etc. It incidentally protects the dies too. Exposed surfaces of the assembly 1 may otherwise be protected at an earlier or later stage of the fabrication process, as discussed earlier. Still, any protective film is removed before applying the cover-film 62 , which is applied after cutting S 2 and before singulation S 8 . Portions of the film 62 shall typically cover the cuts 10 c as well; there is no reason to avoid this since the cover film is chosen so as to allow singulation (that would even substantially complicate the patterning and deposition of the film 62 ).
- the cover-film applied is a dry-film resist 62 .
- the dry-film resist may preferably comprise an epoxy resin, be a laminate sheet, and/or have a Young's modulus between 3 and 5 gigapascal. Fulfilling any of these conditions contribute to improve characteristics of the cover-film.
- Polyepoxide films have been found to be best suited for several applications, especially when cleaving the blocks by hand. They notably are rigid enough to tent over microstructures (e.g., microchannels 20 ) without collapsing, which microstructures typically are 100-200 ⁇ m wide.
- cover film 62 is brittle enough to allow breaking, and nonetheless has remarkable adhesion to the surface, thereby preventing delamination and leaking. Most practical is to use a cover film initially provided as a laminate sheet to apply it on the surface of the substrate, as discussed below in detail.
- any rigid enough cover film can be contemplated, like silicon or thin glass.
- the Young's modulus of the cover should typically be between 3 and 200 gigapascal. If an optical clear material is required, glass can be used, but it results in less clean parting breaks, interfaces, etc., than dry-film resists, which usually are optically clear and therefore enable subsequent observation/detection.
- the thickness of the dry-film resist 62 applied is between 10 and 100 ⁇ m. Satisfactory results were already obtained with 14 ⁇ m thick films but optimal results were obtained for thicknesses of about 50 ⁇ m ⁇ 20 ⁇ m.
- the cover film itself shall preferably exhibit less than 5% thickness variation, to ensure satisfactory adhesion and sealing.
- a much preferred material is a dry-film resist consisting of 50 ⁇ m thick DF-1050 from Engineered Material Systems, Inc. EMS, Ohio, USA, which provides remarkable mechanical performance for applications as discussed herein.
- This material essentially comprises Epoxy Resin, 6-Glycidyloxynapht-1-yl oxymethyloxirane, and Antmony.
- applying S 5 -S 7 the cover film 62 is carried out as follows:
- a practical way of applying the film 62 is indeed to press it indirectly against the surface via another layer 61 .
- Alignment of the dry-film 62 with the chip may be done manually e.g., using markers on both the chip surface and any of the films 61 , 62 or thanks to any suitable alignment tool.
- Steps S 3 a - c may notably include a step of patterning S 3 c the cover film 62 .
- This is preferably achieved by photolithography, cutting, punching or laser ablation, and preferably prior to applying S 5 the patterned cover film 62 .
- This makes it possible to obtain a cover film 62 , e.g., a dry-film resist, that comprises openings 62 o forming patterns that correspond to structures of the microfluidic chip assembly, already present or to be subsequently fabricated. That is, the patterns must correspond to, i.e., functionally match features already present 20 or to be later fabricated on the exposed surface of the assembly 1 .
- a dry-film patterned such as to later allow for providing electrical contact openings 62 , liquid loading pad, air vents, etc., which features may be fabricated or mounted at a later stage.
- the patterns correspond to features 20 already present and no additional features are to be fabricated, such that the chips are ready for use after application of the cover-film 62 and after singulation (autonomous chips).
- the film 60 may also be initially provided S 3 a as a dry-film resist sandwiched between two backing films 61 , 63 .
- One 63 of the two backing films is removed S 3 b prior to or after patterning S 3 c the dry-film resist 62 , while the other one of the backing film is kept for lamination. That is, in some variants, the film 63 is removed prior to patterning, while in other variants, the whole stack 61 - 63 is patterned (contrary to the apparent order in FIG. 3 ), which may be easier and cleaner, depending on the patterning technique used.
- Intermediate solutions are also possible. For example:
- microfluidic chip fabrication mainly involving rapid prototyping of polymers and silicon or glass micromachining.
- chips are prepared one-by-one for research purposes or fabricated by wafer-level bonding and then diced.
- the last fabrication steps usually involve wet media such as cooling water for the dicing saw and require laborious chip handling.
- Special care is required, in particular when fabricating capillary-driven microfluidic chips because adversary filling of liquids present during the dicing, cleaning, and surface treatment steps can contaminate the channels.
- embodiments of the present invention provide particularly high-throughput microfluidic chip fabrication and singulation, the essential steps being carried out at substrate-level e.g., wafer-level, eliminating tedious chip-by-chip processing.
- the singulation of the ready-to-use chips may result to be as easy as breaking a chocolate bar.
- a particularly preferred embodiment is to partially cut the wafer up to about half the wafer thickness (e.g., 525 ⁇ m) using a dicing saw, S 2 .
- the partially diced wafer is then cleaned and a pre-patterned dry-film resist 61 - 62 is aligned and laminated S 5 on top of the channels 20 .
- a covered microfluidic body is obtained, S 6 .
- chips can be singulated by breaking through the dicing cuts, S 8 .
- cover film 62 As discussed already, the mechanical properties of the cover film 62 are of particular importance.
- An ideal cover material 62 should, at least for particular applications, (i) be rigid enough to tent over the channels without collapsing, (ii) be brittle enough to allow breaking, (iii) have good adhesion to the surface to prevent delamination and leaking, (iv) enable patterning by cutting, punching, or photolithography, and (v) not interfere with the wettability of the channels. All these requirements are nicely met with the preferred example of material given above, i.e., a ⁇ 50 ⁇ m thick DF-1050 from Engineered Material Systems, Inc. EMS.
- the blocks 14 may notably comprise microfluidic microchannels 20 on face F of the substrate, as part of the microstructures.
- the average depth or cross-sectional diameter of such microchannels 20 is preferably between 5 and 50 ⁇ m, and more preferably between 10 and 20 ⁇ m. Still, the microchannel depth is typically constant.
- a microchannel shall typically have a width between 100-200 ⁇ m. Still, a 50 ⁇ m width may be used for reduced sections, while up to 500 ⁇ m can be contemplated for the wider sections.
- the channels are typically a few mm long, e.g., 4 mm or more.
- the channels may be grooved (e.g., etched) into the superficial thickness of the body 10 , or a layer 30 adjacent thereto, or provided within a layer covering the body, such as a dry-film resist or a SU-8 film coated and patterned for this purpose, as known per se.
- microfluidics generally have deep structures, i.e. around a few micrometer, up to 20 micrometers or even more. In many cases, 5 micrometers is already considered as a small depth in microfluidic applications. There are multiple reasons: such a small depth can generate a large hydraulic resistance on a liquid and can block or become clogged with microbeads and particles. Such a small depth can also be incompatible with samples containing cells.
- Preferred substrates comprise a wafer as a main body 10 , e.g., wafers of silicon, germanium, gallium arsenide GaAs, other compound III-V or II-VI materials, as it may allow for benefiting from experience accumulated for integrated circuit IC processes.
- IC processes can usually not be used as such to fabricate microfluidic structures, especially as contemplated herein. Rather, they need be adapted to achieve the typical dimensions required for such structures, as discussed above.
- glass can be used as well, instead of semiconductor wafers. Less preferred variants would use other materials such as metals or other materials commonly used in microfluidics.
- the wafer may for instance be a ⁇ 100> Si wafer with a flat in the ⁇ 110 > direction; thus the top surface has a normal in ⁇ 100> direction.
- the face F is accordingly parallel to (100) planes in that case, i.e., orthogonal to the (100) direction in the basis of the reciprocal lattice vectors (Diamond structure for Si).
- the fabrication methods discussed above may comprise a further step of separating (singulation) at least one of the blocks 14 , 14 a from the package/assembly, to extend to fabrication of individual chips.
- the invention can be embodied as a microfluidic chip package or assembly 1 . Consistently with fabrication methods described earlier, such a package/assembly notably comprises:
- cover film 62 may comprise openings 62 o forming patterns, in correspondence with microfluidic structures of the blocks.
- microfluidic structures may notably comprise:
- microfluidic chip packages or assemblies can be provided to a recipient, who can then easily singulate the blocks, without any specific equipment, e.g., simply by hand, just as one breaks chocolate bars.
- the invention can be embodied as a microfluidic chip (obtainable according to present fabrication methods) or, similarly, from a microfluidic chip package or assembly as discussed above.
- the chip is obtained by separating a covered block 14 from the package or assembly 1 .
- the resulting chip shall therefore exhibit residual marks of partial cut 10 c and residual marks of singulation, such as cleavage planes or parting breaks, at a periphery of a covered block.
- cleavage in a broad sense, applies not only to crystalline substrates (e.g., wafers) but also to non-crystalline substrates such as glass wafers. Residual traces of cuts 10 c look like a polished mirror surface in the case of Si wafer, see FIG. 11 .
- microfluidic chip assembly was notably demonstrated as follows: a microfluidic test structure with a loading pad, a serpentine channel 100 ⁇ m width, and a capillary pump, was fabricated on a 525 ⁇ m thick Si wafer by patterning DuPont PerMX3020 20 ⁇ m thick dry-film resist, to pattern microfluidic channels on top of the Si wafer. After coating a thin photoresist layer for protecting the structures, the wafer was diced to about 250 ⁇ m depth. A 50 ⁇ m thick DF-1050 dry-film resist EMS, USA was cut using a benchtop cutting plotter to create the loading pad and electrical contact openings 62 o ( FIG. 10 a ).
- This cover film was aligned and laminated ( FIG. 10 b ) on the partially diced wafer. Compared to other microfluidic channel sealing techniques such as wafer bonding, the dry-film lamination requires much less time and temperature budget.
- the sealed chips were then separated easily by cleaving the wafer, FIGS. 10 c and d , by hand. Optical inspection of the cleaved chip shows no substantial structural damage on the cover film, see FIG. 11 .
- FIG. 11 is an image showing a slightly tilted microfluidic chip, showing a cut (diced) part (top, neighboring partial cut edge 10 c ) and a cleaved part (bottom, delimited by the cleaved edge 10 s ) of a microfluidic chip.
- the chip is in silicon, with microfluidic structures 24 defined in a photopatterned dry-film resist 32 (PerMX3020). Beyond the loading pad 24 , the chip comprises a serpentine channel (partly visible) and a capillary pump (not visible).
- the DF-1050 layer 62 has the slightly larger circular opening (outer circular opening), and is thicker; the PerMX3020 layer 32 has the smaller inner circular pattern, channel 20 is defined in the PerMX3020 layer 32 in this embodiment.
- Methods described herein can be used in the fabrication of wafer-based microfluidic chips.
- the resulting chips can notably be distributed by the fabricator in raw wafer form (that is, as a single wafer that has multiple unpackaged chips), as a bare die, or in a packaged form.
- a chip is mounted in a single chip package (such as a plastic carrier) or in a multichip package.
- the chip can then be integrated with other chips, or other microfluidic elements (tubing ports, pumps, etc.) even if applications to autonomous chips are preferred, as part of either (a) an intermediate product or (b) an end product.
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US11198119B2 (en) * | 2013-06-28 | 2021-12-14 | International Business Machines Corporation | Fabrication of a microfluidic chip package or assembly with separable chips |
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CN105498868B (zh) * | 2015-11-20 | 2017-10-13 | 华南师范大学 | 一种微流控芯片的封装方法 |
US9770717B1 (en) * | 2016-11-03 | 2017-09-26 | International Business Machines Corporation | Microfluidic chip with bead integration system |
USD849265S1 (en) * | 2017-04-21 | 2019-05-21 | Precision Nanosystems Inc | Microfluidic chip |
WO2018222976A1 (en) * | 2017-06-02 | 2018-12-06 | Warner Babcock Institute For Green Chemistry, Llc | Methods for producing metal oxide films, patterned metal oxide surfaces, and filtration of volatile organic compounds |
US12032286B2 (en) | 2019-06-17 | 2024-07-09 | Asahi Kasei Kabushiki Kaisha | Method for producing multi-layered type microchannel device using photosensitive resin laminate |
CN114177955A (zh) * | 2020-09-14 | 2022-03-15 | 中国科学院大连化学物理研究所 | 一种微流控芯片、模板及制备方法 |
CN114247488B (zh) * | 2021-11-23 | 2023-12-08 | 东胜神州(北京)医学诊断技术有限公司 | 一种袋反应器的制造方法 |
CN115261451A (zh) * | 2022-07-26 | 2022-11-01 | 深圳太古语科技有限公司 | 一种用于测序芯片表面化学处理及封装键合的方法 |
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US11198119B2 (en) * | 2013-06-28 | 2021-12-14 | International Business Machines Corporation | Fabrication of a microfluidic chip package or assembly with separable chips |
Also Published As
Publication number | Publication date |
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US20180361380A1 (en) | 2018-12-20 |
JP6478231B2 (ja) | 2019-03-06 |
DE112014000462T5 (de) | 2015-10-15 |
US20160367984A1 (en) | 2016-12-22 |
JP2016529116A (ja) | 2016-09-23 |
US11198119B2 (en) | 2021-12-14 |
DE112014000462B4 (de) | 2023-06-01 |
GB2531452A (en) | 2016-04-20 |
WO2014207619A1 (en) | 2014-12-31 |
GB201311680D0 (en) | 2013-08-14 |
GB201600188D0 (en) | 2016-02-17 |
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